SMARCAD1 is an ATP-dependent histone octamer exchange factor with de novo nucleosome assembly activity

The adenosine 5'-triphosphate (ATP)-dependent chromatin remodeler SMARCAD1 acts on nucleosomes during DNA replication, repair, and transcription, but despite its implication in disease, information on its function and biochemical activities is scarce. Chromatin remodelers use the energy of ATP hydrolysis to slide nucleosomes, evict histones, or exchange histone variants. Here, we show that SMARCAD1 transfers the entire histone octamer from one DNA segment to another in an ATP-dependent manner but is also capable of de novo nucleosome assembly from histone octamer because of its ability to simultaneously bind all histones. We present a low-resolution cryo-electron microscopy structure of SMARCAD1 in complex with a nucleosome and show that the adenosine triphosphatase domains engage their substrate unlike any other chromatin remodeler. Our biochemical and structural data provide mechanistic insights into SMARCAD1-induced nucleosome disassembly and reassembly.

Automated summary

The study demonstrates that SMARCAD1 is capable of transferring the entire histone octamer from one DNA segment to another in an ATP-dependent manner, as well as de novo nucleosome assembly from histone octamer due to its ability to simultaneously bind all histones. The low-resolution cryo-electron microscopy structure of SMARCAD1 in complex with a nucleosome reveals a unique engagement of its adenosine triphosphatase domains with the substrate, providing mechanistic insights into nucleosome disassembly and reassembly induced by SMARCAD1.